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Abstract:

The invention comprises a method for measuring the relative thickness of
the lipid layer component of the precorneal tear film on the surface of
an eye after distribution of the lipid layer subsequent to blinking.
Light is directed to the lipid layer of a patient's eye with an
illuminator. The illuminator is a broad spectrum light source covering
the visible region and is a lambertion light emitter such that the light
source is specularly reflected from the lipid layer and undergoes
constructive and destructive interference in the lipid layer. The
specularly reflected light is collected and focused using a collector
such that the interference patterns on the tear film lipid layer are
observable. The collector also produces an output signal representative
of the specularly reflected light which is suitable for further analysis,
such as projection on to a high resolution video monitor or analysis by
or storage in a computer. In order to facilitate ease of measurement, the
patient's head may be positioned on an observation platform when the
illuminator directs light to the lipid layer of the patient's eye.

Claims:

1. A method for measuring the thickness of the lipid layer on the surface
of a patient's eye after distribution of the lipid layer subsequent to
blinking comprising the steps of:illuminating the lipid layer of a
patient's eye with a broad spectrum light source illuminator in the
visible region and being a lambertian emitter such that the rays from the
light source are specularly reflected from the lipid layer and undergo
constructive and destructive interference in the lipid layer thereby
producing interference patterns; andan imaging device for observing the
specularly reflected light such that the interference patters on the tear
film lipid layer are observable.

2. The method according to claim 1 wherein the illuminator comprises an
arcuate emitter and wherein the surface of the lambertian emitter is
substantially parallel to the surface of the eye.

3. The method according to claim 1 wherein the specularly reflected light
is observed through a hole defining an opening in the illuminator.

4. The method according to claim 3 wherein the opening in the illuminator
allows for observation of the specularly reflected light from behind said
illuminator.

5. The method according to claim 3 further including the steps of
collecting and focusing the specularly reflected light and the step of
generating an output signal representative thereof operatively associated
with the opening.

6. The method according to claim 5 further including the step of recording
the output signal representative of the specularly reflected light.

7. The method according to claim 6 wherein the step of recording the
output signal representative of the specularly reflected light records in
real time.

8. The method according to claim 5 wherein the step of collecting and
focusing the output signal is produced by use of a camera lens system.

9. The apparatus according to claim 6 wherein the recording is selected
from the group of recording devices consisting of computer memory, video
cassette recording devices, analog recording devices and digital
recording devices.

10. The method according to claim 1 wherein the specularly reflected light
is observed when the patient's head is positioned on an observation
platform.

11. The method according to claim 2 wherein the arcuate emitter is
constructed and arranged such that the light rays emitted therefrom
strike the surface of the eye such that Snell's Law is satisfied and
produces an observable area of interference on the surface of the eye.

12. The method according to claim 1 wherein said illuminator further
includes a plurality of spaced apart light emitting diodes adapted to
emit light in the visible region; anda diffuser for diffusing the light
emitted by the respective light emitting diodes positioned between the
light emitting diodes and the surface of the eye and further, wherein the
diffuser is arcuate such that the light rays emitted therefrom strike the
surface of the eye such that Snell's law is satisfied with respect to the
acceptance angle of the camera lens system to produce an observable area
of interference on the eye.

13. The method according to claim 11 wherein the light rays that generate
the visible viewing area of interference are substantially normal to the
surface of the eye.

14. The method according to claim 1 wherein said illuminator has a total
radiated power of less than 1 W.

15. A method for measuring the thickness of the lipid layer on the surface
of an eye after distribution of the lipid layer subsequent to blinking
comprising the steps of:illuminating the lipid layer of a patient's eye
with a broad spectrum light source illuminator in the visible region and
being a lambertian emitter such that the light source is specularly
reflected from the lipid layer and undergoes constructive and destructive
interference in the lipid layer thereby producing interference patters in
the tear film and further, wherein the total light emitted from the
surface of the illuminator is less than 10 μW/mm2; andobserving
the specularly reflected light.

16. The method according to claim 15 wherein the illuminator further
includes an arcuate emitter and wherein the surface of the emitter is
substantially parallel to the surface of the eye.

17. The method according to claim 15 wherein the specularly reflected
light is observed through a hole defining an opening in the illuminator.

18. The method according to claim 17 wherein the opening in the
illuminator allows for observation of the specularly reflected light from
behind said illuminator.

19. The method according to claim 17 further including the step of
collecting and focusing the specularly reflected light and the step of
generating an output signal representative thereof operatively associated
with the opening.

20. The method according to claim 19 further including the step of
recording the output signal representative of the specularly reflected
light.

21. The method according to claim 20 wherein the step of recording the
output signal representative of the specularly reflected light records in
real time.

22. The method according to claim 19 wherein the steps of collecting and
focusing is produced by the use of a camera lens system.

23. The method according to claim 20 wherein the step of recording is
selected from the group of recording devices consisting of computer
memory, video cassette recording devices, analog recording devices and
digital recording devices.

24. The method according to claim 15 wherein the specularly reflected
light is observed when the patient's head is positioned on an observation
platform.

25. The method according to claim 15 wherein the arcuate emitter is
constructed and arranged such that the light rays emitted therefrom
strike the surface of the eye such that Snell's law is satisfied and an
observable area of interference is produced on the eye.

26. The method according to claim 15 wherein the illuminator further
includes a plurality of spaced apart light emitting diodes adapted to
emit light in the visible region; anddiffusing the light emitted by the
respective light emitting diodes and further, wherein the illuminator is
arcuate such that the light rays emitted from the lambertian emitter
strike the surface of the eye such that Snell's law is satisfied with
respect to the acceptance angle of said camera lens system to produce an
observable area of interference on the eye.

27. The method according to claim 25 further including the step of
collecting the specularly reflected light and focusing the specularly
reflected light generates an output signal representative thereof.

28. The method according to claim 25 wherein the illuminator has a total
radiated power of less than 1 W.

29. The method according to claim 25 wherein the light rays that generate
the visible viewing area of interference are essentially normal to the
surface of the eye.

30. A method for measuring the thickness of the lipid layer on the surface
of a patient's eye after distribution of the lipid layer subsequent to
blinking comprising the steps of:illuminating the lipid layer of a
patient's eye with broad spectrum light source illuminator in the visible
region and being a uniform illumination lambertian emitter such that the
light source is specularly reflected from the lipid layer and undergoes
constructive and destructive interference in the lipid layer; and further
wherein the illuminator illuminates the patients face, but wherein only
an area below the pupil satisfies Snell's law; andobserving the area of
interference in specularly reflected light on the tear film lipid layer
below the pupil.

31. The method according to claim 30 further including the steps of
collecting and focusing the specularly reflected light such that the
interference patterns on the tear film lipid layer are observable.

32. The method according to claim 30 wherein the illuminator illuminates
an area of the patient's eye and wherein the area having viewable
interference fringes is located below the pupil.

33. The method according to claim 32 wherein the area having viewable
interference fringes is an area of at least 12.5 mm.sup.2.

34. The method according to claim 30 wherein the illuminator has a total
illumination intensity of less than that which would induce reflex
tearing or cause a proprioceptive response to occur.

35. The method according to claim 34 wherein the illuminator has a total
illumination intensity of between about 1 μW/mm2 and 15
μW/mm2 at the surface of the illuminator.

36. The method according to claim 32 wherein the specularly reflected
light is observed when the patient's head is positioned on an observation
platform.

37. The method according to claim 30 further including the step of
recording the observable area of interference of the specularly reflected
light.

38. The method according to claim 37 wherein the step of recording the
observable are of interference records in real time.

39. The method according to claim 37 wherein the step of recording is
selected from the group of recording devices consisting of computer
memory, video cassette recording devices, analog recording devices and
digital recording devices.

40. The method according to claim 31 wherein the step of collecting and
focusing the specularly reflected light generates an output signal
representative thereof.

41. The method according to claim 30 wherein the illuminator comprises an
array of light emitting diodes and a diffuser positioned between the
respective diode array and the lipid layer of the tear film.

42. The method according to claim 41 where the diffuser is arcuate such
that the light rays emitted from the lambertian emitter strike the
surface of the eye such that Snell's law is satisfied and an observable
area of interference is produced on the eye.

43. A method for measuring the thickness of the lipid layer on the surface
of an eye after distribution of the lipid layer subsequent to blinking
comprising the steps of:illuminating the lipid layer of a patient's eye
with a broad spectrum light source illuminator in the visible region and
being a uniform illumination lambertian emitter such that the light
source is specularly reflected from the lipid layer and undergoes
constructive and destructive interference in the lipid layer and wherein
the light emitted from the illuminator travels directly to the lipid
layer without reflection and strikes the lipid layer; andcollecting and
focusing the specularly reflected light such that the interference
patterns on the tear film lipid layer are observable.

44. The method according to claim 43 wherein the illuminator illuminates
an area of the patient's eye and wherein the area having viewable
interference fringes is located below the pupil.

45. The method according to claim 43 wherein the area having viewable
interference fringes in an area of at least 12.5 mm.sup.2.

46. The method according to claim 43 wherein the illuminator has a total
illumination intensity of less than what which would induce reflex
tearing or cause a proprioceptive response to occur.

47. The method according to claim 43 wherein the illuminator has a total
illumination intensity of between about 1 μW/mm2 and 15
μW/mm2 at the surface of the illuminator.

48. The method according to claim 43 wherein the illuminator has a total
radiated power of less than about 1 W.

49. The method according to claim 44 wherein the specularly reflected
light is observed when the patient's head is positioned on an observation
platform.

50. The apparatus according to claim 43 further including the step of
recording the observable area of interference of the specularly reflected
light.

51. The apparatus according to claim 50 wherein the step of recording the
observable area of interference records in real time.

52. The apparatus according to claim 51 wherein the step of recording is
selected from the group of recording devices selected from the group
consisting of computer, video cassette recording devices and digital
recording devices.

53. The method according to claim 44 wherein the step of collecting and
focusing the specularly reflected light generate an output signal
representative thereof.

54. The method according to claim 43 wherein the illuminator comprises an
array of light emitting diodes and a diffuser positioned between the
respective diode array and the lipid layer of the tear film.

55. The method according to claim 54 where the diffuser is arcuate such
that the light rays emitted from the lambertian emitter strike the
surface of the eye such that Snell's law is satisfied and an observable
area of interference is produced on the eye.

Description:

[0002]This invention relates generally to the field of measurement of the
tear film thickness on the precomeal surface of the eye and more
particularly, to the measurement of the thickness of the outermost layer
of the tear film, i.e., the lipid layer.

BACKGROUND OF THE INVENTION

[0003]The human precomeal tear film is comprised of three primary layers,
each of which serves a specific function. The innermost layer of the
precomeal tear film provides a protective environment for the superficial
epithelial cells of the cornea and helps protect against microbes and
foreign bodies. The outer surface of the precomeal tear film is the
primary refracting surface of the eye. Its surface tension helps to
smooth this surface, thus improving the optical quality of the image
ultimately impacting the retina. Additionally, the precomeal tear film
provides a lubricating function during blinking. These structures are
often disrupted in dry eye conditions, which are some of the most common
ophthalmic disorders seen by eye-care practitioners. Dry eye disorders
and/or disease can lead to premature breakup of the tear film after a
blink, leading to damage of the superficial epithelium which may result
in discomfort and be manifested as optical blur. In addition, the ability
of a patient to wear contact lenses is a direct function of the quality
and quantity of the tear film, and dry eye disorders and/or disease
therefore has a significant impact on contact lens wear parameters.

[0004]The precomeal tear film is comprised of an inner mucin layer, a
middle aqueous layer, and an outermost thin lipid layer. Various
treatments are used in an attempt to alleviate dry eye symptoms. For
example, it has been proposed to treat certain dry eye conditions by the
application of heat and pressure to unclog meibomian glands, or with
pharmaceutical methods to unclog meibomian glands and to stimulate tear
production.

[0005]Notwithstanding the foregoing, it has been a long standing and
vexing problem for clinicians and scientists to objectively demonstrate
an improvement in the precomeal tear film thickness at the conclusion of
the proposed treatment. Further, many promising treatments for dry eye
have failed to receive approval from the United States Food and Drug
Administration due to the inability to demonstrate clinical effectiveness
to the satisfaction of the agency.

[0006]In response to the foregoing long felt need, various methods of
measuring the thickness of the precomeal tear film, and specifically the
lipid layer thereof have been proposed. For example, Korb, one of the
inventors of this invention provided an overview and background of his
invention of a specular reflection microscope system that allowed
quantification of the tear film lipid layer thickness based on the
interference colors of the lipid layer. This system included a
hemi-cylindrical broad spectrum illumination source with heat absorbing
filters, a binocular microscope with a Zeiss beam-splitter providing 70%
light to a high resolution video camera, a VHS recorder, and a high
resolution 20-inch color monitor. Following calibration with Eastman
Kodak color reference standards (Wratten filters), the static and dynamic
appearance of the lipid layer was observed before and after blinking.
During the observation period, the subject was instructed to blink
naturally while gazing at a fixation target. For purposes of quantization
and standardization, a specific region of the tear film was designated
for analysis. This area encompassed a zone approximately one mm above the
lower meniscus to slightly below the inferior pupillary margin, averaging
7-8 mm wide and 2.5 mm in height. The dominant color of the specularly
reflected light within this designated area was used as the basis for
assigning lipid layer thickness values. Thickness values were assigned to
specific colors on the basis of prior work on tear film lipid layer
interference colors (McDonald, 1969; Nom.; 1979; Guilon, 1982; Hamano et
al., 1982) and are summarized in Table 1. To confirm the lipid layer
thickness values assigned to each subject's tear film lipid layer,
recordings were independently graded by two observers masked as to
subject identity. (Korb, D R, Baron D F, Herman J P, et al., Tear Film
Lipid Layer Thickness as a Function of Blinking, Cornea 1994:13:354-9).
While the foregoing apparatus was effective in measuring improved lipid
layer thickness, measurement inaccuracies were nevertheless introduced
into the system. Working backwards, the color monitor had to be provided
with a sufficient input signal to enable the lipid layer to be imaged on
to the monitor screen. The foregoing thus required a minimum illumination
to be provided to the slit lamp, of which 70% was directed to the high
resolution video camera. This, in turn, dictated the minimum amount of
light required to illuminate the corneal surface. Thus, the amount of
light required to make the foregoing system operational was not optimum
as it interfered with the naturally occurring tear film as the heat
generated by the light caused tear film evaporation. Further, the amount
of light required to make the system functional caused some degree of
reflex tearing.

[0007]Another apparatus for measuring the tear film is disclosed in
European Patent Application EP 0 943 288 assigned to Kowa Company, Ltd.
of Japan. The application discloses an apparatus for the non-contact
measurement of the quantity of lacrimal fluid collected on the lower
eyelid. According to the invention, tear volume is calculated from a
measurement of the volume of fluid pooled at the lid eye meniscus. While
knowledge of the total volume of fluid may be of some use to eye-care
practitioners, it does not specifically measure the lipid layer thickness
or its improvement as the result of a particular treatment regimen.

[0008]U.S Pat. No. 4,747,683 to Marshall G. Doane discloses a Method and
Device for in Vivo Wetting Determinations wherein a contact lens is
illuminated with coherent light and the pre-lens tear film is imaged in
such a way as to form an interference pattern. The image formed thereby
is recorded and the tear film thickness is determined by correlating the
interference bands of the recorded image. A coherent light source and a
camera are focused at the pre-lens film to image specularly reflected
light from the front and rear surfaces of the tear film. A film motion
analyzer provides numerical coordinates of interference bands, and a
microprocessor analyses the coordinates to provide a quantitative measure
of lens position or wetting characteristics. Again, while knowledge of
the tear film thickness covering the contact lens surface may be useful
in the context of contact lens fitting, the Doane apparatus does not
specifically measure lipid layer thickness on the natural eye.

[0009]Another instrument that purports to measure tear film lipid layer
thickness is the Tearscope Plus manufactured by Keeler Instruments Inc.,
of Broomall, Pa. and Berkshire, UK. More specifically, the Tearscope is a
hand-held or slit lamp mounted device that comprises a tubular housing
which contains a coaxially mounted cylindrical light source. The interior
bore of the housing is covered with a cylindrical diffuser plate that
diffuses the light. In use, the eye-care practitioner places one end of
the tube proximate the patient's eye thus illuminating the whole eye,
including the pupil, and observes the interference patterns on the pupil
surface through the opposite end of the tube. The color of the
interference pattern generated by blinking is then correlated to tear
film thickness. The Tearscope is not without its inherent drawbacks and
deficiencies as the process by which the eye is illuminated and the
measurement is made introduces error which is diagnostically
unacceptable. For example, the proximity of the illuminator to the eye
surface when combined with the light intensity required to obtain a
viewable interference pattern can cause reflex tearing. In addition, the
illumination system employed illuminates the entire eye, including the
pupil. Thus, light from the Tearscope is directed on to the retinal
surface which, in turn causes a proprioceptive response which also skews
measurement accuracy.

[0010]In view of the foregoing, it is an object of the present invention
to provide a method and apparatus that overcomes the drawbacks and
deficiencies of the prior art.

[0011]Another object of the present invention is to provide a method and
apparatus that allows the accurate measurement of the thickness of the
lipid layer component of the precorneal tear film.

[0012]A further object of the present invention is to provide a method and
apparatus wherein the lipid layer thickness of the precorneal tear film
may be measured without the introduction of reflex tearing.

[0013]A still further object of the present invention is to provide a
method and apparatus that enhances contrast and thereby the observability
and measurablity of the lipid layer thickness of the precorneal tear
film.

[0014]Yet another object of the present invention is to provide a method
and apparatus for measuring the lipid layer thickness of the precorneal
tear film using a low level of light in order to minimize tear film
evaporation that can alter the measurement.

[0015]Another object of the present invention is to provide a method and
apparatus for measuring the lipid layer thickness of the precorneal tear
film wherein the patient is comfortable during the examination.

[0016]Another object of the present invention is to provide a method and
apparatus for measuring the lipid layer thickness of the precorneal tear
film that minimizes light entering the pupil to minimize reflex tearing
and proprioceptive responses that can alter the measurement.

SUMMARY OF THE INVENTION

[0017]In accordance with the foregoing, the invention comprises a method
for measuring the thickness of the lipid layer component of the
precorneal tear film on the surface of an eye after distribution of the
lipid layer subsequent to blinking. Light is directed to the lipid layer
of a patient's eye by use of an illuminator which produces specularly
reflected light rays. The illuminator is a broad spectrum, large area
lambertian light source covering the visible region, the rays of which
are specularly reflected from the lipid layer and undergo constructive
and destructive interference in the lipid layer. The specularly reflected
light is collected and focused such that the interference patterns on the
tear film lipid layer are observable. An output signal is produced that
is representative of the specularly reflected light which is suitable for
further analysis, such as projection on to a high resolution video
monitor or analysis by or storage in a computer. Alternatively, the
interference patterns of the specularly reflected light may be directly
observed by the clinician and recorded. In order to facilitate ease of
measurement, the patient's head may be positioned on an observation
platform, for example, a slit lamp stand, when the illuminator directs
light to the lipid layer of the patient's eye.

[0018]In a first embodiment of the invention, the illuminator is sized to
show the interference pattern of the lipid layer over the whole eye,
(termed herein the "whole eye illuminator"), with the provision that the
intensity of the light entering the pupil and striking the retina are
below the threshold at which appreciable measurement error is introduced,
i.e., the reflex tear and proprioceptive responses are not activated.
Observation of the interference pattern in the preferred embodiment is
through an opening in the illuminator.

[0019]In a second embodiment of the invention, the illuminator is sized to
show the interference pattern of the lipid layer below the pupil, (termed
herein the "half eye illuminator"), such that the intensity of the light
entering the pupil is extremely low, thus avoiding the introduction of
virtually all system-induced inaccuracy. Observation of the interference
pattern in this second embodiment is from above the illuminator.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020]These and other features will be understood with reference to the
figures, in which

[0021]FIG. 1 is a side view of the tear film analyzer according to the
present invention mounted to a stand with a patient positioned for
viewing of interference fringes on the lipid layer of the eye. The
illuminator portion is shown as a vertical cross section through the
center.

[0022]FIG. 2 is a plan view of the tear film analyzer according to the
present invention mounted to a stand with a patient positioned for
viewing of interference fringes on the lipid layer of the eye.

[0023]FIG. 3a is a side view of a second embodiment of the tear film
analyzer according to the present invention mounted to a stand with a
patient positioned for viewing of interference fringes on the lipid layer
of the eye. The illuminator portion is shown as a vertical cross section
through the center.

[0024]FIG. 3b is a side view of the second embodiment of the tear film
analyzer according to the present invention mounted to a stand and tilted
with a patient positioned for viewing of interference fringes on the
lipid layer of the eye. The illuminator portion is shown as a vertical
cross section through the center.

[0025]FIG. 4a is a plan view of the second embodiment of the tear film
analyzer according to the present invention mounted to a stand with a
patient positioned for viewing of interference fringes on the lipid layer
of the eye.

[0026]FIG. 4b is a plan view of the second embodiment of the tear film
analyzer according to the present invention mounted to a stand and tilted
with a patient positioned for view of interference fringes on the lipid
layer of the eye.

[0027]FIG. 5a is a plan view of the second embodiment of the tear film
analyzer according to the present invention illustrating the illuminator
surface that produces the outer edges of the viewable area of
interference fringes.

[0028]FIG. 5b is a side view of the second embodiment of the tear film
analyzer according to the present invention illustrating the illuminator
surface vertically positioned below the plane of the pupil and showing
the outer edges of the viewable area of interference fringes.

[0029]FIG. 5c is a side view of the second embodiment of the tear film
analyzer according to the present invention illustrating the illuminator
surface positioned below the plane of the pupil and tilted at an angle
and showing the outer edges of the viewable area of interference fringes.

[0030]FIG. 6 is a perspective view, partially exploded, of the full eye
illuminator according to the present invention.

[0031]FIG. 7 is a plan view, sectioned horizontally through the center of
the viewing hole of the full eye illuminator according to the present
invention.

[0032]FIG. 8 is an end view, sectioned vertically through the center of
the full eye illuminator according to the present invention.

[0033]FIG. 9 is a perspective view, partially exploded of the half eye
illuminator according to the present invention.

[0034]FIG. 10 is a plan view with the top removed of the half eye
illuminator according to the present invention.

[0035]FIG. 11 is an end view, sectioned vertically through the center of
the half eye illuminator according to the present invention.

[0036]FIG. 12 is a front view of the surface of an eye and illustrating
schematically the area defined by the extreme lambertion rays wherein
interference patterns are viewable.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037]While the present invention will be described more fully hereinafter
with reference to the accompanying drawings, in which particular
embodiments are shown, it is to be understood at the outset that persons
skilled in the art may modify the invention herein described while still
achieving the favorable results of this invention. Accordingly, the
description which follows it to be understood as a broad teaching
disclosure directed to persons of skill in the appropriate arts and not
as limiting upon the present invention.

[0038]In a first embodiment best shown in FIGS. 1, 2 and 6-8, referred to
herein as the "full eye illuminator", the present invention broadly
comprises illuminating the lipid layer of the patient's eye and observing
the light specularly reflected therefrom. A second embodiment best shown
in FIGS. 3a, 3b, 5a-5c and 9-11, referred to herein as the "half eye"
illuminator is shown. The mode of operation of the two embodiments is
substantially identical and they will therefore be described together
using the same reference numerals and where differences between the
embodiments occur, they will be discussed.

[0039]The lipid layer of a patient's eye is illuminated with an
illuminator 100 and comprises a large area broad spectrum light source
covering the visible region. The illuminator 100 is a lambertian emitter
adapted to be positioned in front of the eye on a stand 300. As employed
herein the terms "lambertion surface" and "lambertian emitter" are
defined to be a light emitter having equal intensity in all directions.
The light source comprises a large surface area emitter, arranged such
that rays emitted from the emitter are specularly reflected from the
lipid layer and undergo constructive and destructive interference in the
lipid layer. An image of this surface is the backdrop over which the
interference image is seen and it should be as spatially uniform as
possible. The illuminator 100 illuminates a large area of the face which
creates a 2.5 mm high by 5 mm long viewable area centered beneath the
pupil 310 (see FIG. 12) which is adequate for lipid layer thickness
determination and correlation to dry eye. By "viewable area" it is meant
the active area that satisfies the criteria for viewing interferences
fringes; i.e., approximately 2.5 mm×7 mm for the half eye
illuminator. Full-eye illumination, excluding the pupil area, reveals
additional information about the whole eye pattern of lipid distribution.

[0040]The geometry of the illuminator 100 can be most easily understood by
starting from the camera lens and proceeding forward to the eye and then
to the illuminator. The fundamental equation for tracing ray lines is
Snell's law:

N1 Sin o1=N2 Sin o2, 1)

where N is the refractive index of the medium containing the ray, and o is
angle of the ray relative to the normal from the surface. For a reflected
ray that doesn't enter the lipid layer, N1=N2, and

1=o2 2)

Under these conditions, Snell's law reduces to the classical "angle of
incidence is equal to the angle of reflectance" statement.

[0041]According to the present method, it is necessary to determine only
the extreme rays (the ones at the outermost boundary of the desired
viewing area) to define the area of the illuminator. Since the surface of
that portion of the eye to be examined is approximately spherical, a line
drawn from the camera lens (or the observer's eye) to the edge of the
viewing area on the observed eye will reflect at the same angle on the
other side of the line normal to the eye surface at the point of
intersection of the line with the eye. When the half eye illuminator
used, it may be tilted to better accommodate the nose and illuminate a
larger area of the inferior lipid layer. Notwithstanding the foregoing,
experimentation using the half eye illuminator has shown that a tilt of
10° to as much as 30° is still functional. Returning now to
the full eye illuminator, as best shown in FIGS. 1 and 2, it will be seen
that facial features block some rays from reaching the surface of the
eye. The nose, cheeks, eyebrows, and eyelids block rays, causing shadows
on the eye surface. Positioning the illuminator for maximum area exposure
is unique to each patient's facial structure. The mechanical dimensions
(height and width) of the illuminator may be extended to cover the
biometric range of facial features of the target population.

[0042]The illuminator 100 is a broad spectrum light source covering the
visible region between about 400 nm to about 700 nm. In the model that
was constructed, high efficiency, white Light Emitting Diodes ("LEDs")
120 were used that have a 50° forward projection angle, 2500 mcd
typical intensity, and 5 mm diameter (part number NSPW510CS, available
from Nichia Corporation, Wixom, Mich.). Other LEDs could be added to the
present invention to enhance the spectral width in the near UV or near IR
regions. The light emitting array platform 130 (FIGS. 6, 7) into which
the LEDs are mounted had a curved surface, subtending an arc of
approximately 130° from the optical axis of the eye (see FIG. 5a).
Approximately 96 LEDs spaced apart in a grid pattern with 6 rows and 16
columns were connected in parallel/series combinations and connected to
an appropriate power supply, well known to those skilled in the art and
therefore, not shown. A housing is formed around the LED array platform
130 by a pair of side panels 135, bottom and top panels 140, rear panel
145 and the diffuser means or diffuser 150. The respective diffuser 150,
LED platform 130, and rear panel 145 are flexible and fit within grooves
147 located in the top and bottom panels 140 and the end pieces 135. The
entire assembly is snapped together and the side panels 135 are then
screwed to top and bottom panels 140. While the illumination means 100
illustrated in the figures is curved or arcuate and has a radius of 7.620
inches from the center of the eye under examination, it could be flat as
long as it subtends 130° around the eye. A curved surface is more
efficient in doing this, as the geometry yields a smaller device which is
easier for the practitioner to use in a clinical setting.

[0043]The total power radiated from the illuminator 100 must be kept to a
minimum to prevent accelerated tear evaporation. In addition, air
currents generated by heating or cooling systems can also cause excess
evaporation and must be minimized (preferably eliminated) to maintain
measurement accuracy. The brightness, or intensity, measured in
μW/mm2, entering the pupil can cause reflex tearing, squinting,
and other visual discomforts, all of which affect measurement accuracy.
For a full-eye illuminator, the curved lambertian emitter includes a
centrally positioned hole defining an opening 160 through which the means
for collecting and focusing the specularly reflected light, i.e., a
camera, eye, or other lens 200, is positioned. The opening 160 in the
center substantially prevents direct illumination from entering the pupil
of the test eye. While less than optimal, the opening 160 could be
located in other parts of the illuminator. The other eye, however, has
the full light intensity entering the pupil. If the illumination
intensity is low enough, the exposed eye does not react. The exposed eye
may also be occluded with a mask, or the illuminator may be segmented so
that parts of the surface are not illuminated. The half-eye illuminator
stops below the centerline of the eye and does not directly illuminate
either pupil or stated otherwise, light rays can only enter the pupil
obliquely and do not impinge on the retina. The current full-eye
illuminator has a brightness or illumination intensity of between about 3
μW/mm2 and 15 μW/mm2 with about 4.5 μW/mm2 at the
surface of the illuminator being preferred, which is held 1-2 inches from
the eye. The total radiated power is less than 1 W and preferably no more
than 400 mW. Brightness above about 6 μW/mm2 becomes
uncomfortable to the second eye if it enters the pupil so as to impinge
directly on the retina. The front surface of the illuminator is the
lambertian emitter, i.e., all points on the extended illuminator surface
are lambertian emitters, and comprises a flexible white translucent
acrylic plastic sheet 150 approximately 1/16 inch thick that serves the
function of diffusing the light emitted from a plurality of LED point
sources and transforming them into the uniform Lambertian emitter.

[0044]In order to prevent alteration of the proprioceptive senses and
reduce heating of the tear film, it is important to minimize the incident
power and intensity on the eye and thus, the step of collecting and
focusing the specularly reflected light is carried out by a high
sensitivity color camera 200. The video camera, slit lamp or other
observation apparatus 200 is positioned in opening 160 and is also
mounted on stand 300 as shown in FIG. 2 or in the case of the half eye
illuminator positioned above the emitter as per FIGS. 3a and 3b. Detailed
visualization of the image patterns requires collecting the specularly
reflected light and focusing the specularly reflected light such that the
interference patterns from the lipid layer are observable. Good digital
imaging requires a CCD video camera having a resolution of up to
1280×1024 pixels and at least 15 Hz frame rate to show the
progression of lipid interference patterns as they spread across the eye.
The AVT Dolphin 145C, 2/3 inch, CCD camera with 6.45 μm square pixels
meets the requirements and outputs a signal representative thereof which
may serve as the input signal to any one of a number of devices such as a
video monitor (preferably high resolution) or a computer for analysis
and/or archiving purposes.

[0045]The lens system employed in the instant tear film analyzer images a
15-40 mm dimension in the sample plane (the eye) onto the active area of
the CCD detector (e.g. 13 mm horizontal dimension for a 2/3 in. CCD). The
lens f-number should be as low as practical to capture maximum light and
minimize the illumination power needed for a good image. The lens chosen
for the half-eye and full-eye systems is the Navitar Zoom 7000 close
focus zoom lens for 2/3in. format CCDs. At lower magnification (25-40 mm
field of view), the eye and lids can be examined to observe the
relationship of the blink to the lipid layer thickness. A more detailed
analysis of the lipid layer can be obtained with a slightly higher
magnification showing a 15-25 mm field of view.

[0046]The lipid layer thickness is not uniform and is classified on the
basis of the most dominant color present in the interference pattern. It
is believed that the lipid layer for most individuals cannot exceed 180
nm, and since thicker lipid layers provide better protection from
evaporation than thinner lipid layers, thicker lipid layers provide
greater protection against the development of dry eye states. Thinner
lipid layers are associated with dry eye states and dry eye symptoms,
particularly if the lipid layer thickness is less than 75 nm.

[0047]The present system displays the interference patterns from white
light incident on the lipid layer film. The relation between the colors
of the interference pattern and the lipid layer thickness (LLT) are shown
in Table 1.

[0048]Extensive research has established that thicker films are indicated
by a blue and brown color, mid-thickness films are indicated by a yellow
color, thinner films are indicated by a grey-yellow color, and very thin
films exhibit a gray scale of different densities with white representing
the thinnest. It is believed in color photometry, brown can be obtained
in an additive process by mixing small intensities of red and green, or
orange and blue, basically the opposite ends of the visible light
spectrum. Alternatively, brown can be obtained in a subtractive process
by filtering out the central yellow-green colors from the white spectrum,
leaving a blue-orange mix.

[0049]It has not been verified why the wavelengths of light observed in
the interference film are inverse to the film thickness, but extensive
clinical testing has led the inventors to the belief and the theory that
destructive interference is the dominant process. The closer the
wavelength is to the film thickness, the greater the interference, so
yellow-red interference will have the strongest effect in a thicker film.
However, thicker films appear blue, so it is postulated that red
wavelengths are removed from the incident light spectrum by destructive
interference and the reflected light appears blue.

[0050]For a thinner film, blue will have a stronger interference. Since
the thinner films appear reddish, it is assumed that the blue is removed
by destructive interference. From this, we assume that the color seen is
the broadband surface reflection with the dominant interference color
band removed. That is, interference subtracts the portion of the spectrum
indicative of the film thickness from the reflected light, leaving the
complementary colors. This is the best explanation known to the inventors
of how brown is obtained from a system of this type. It must be noted
that the thickness of the lipid layer on the eye is much smaller than all
the wavelengths of visible light. Therefore, full wavelength interference
patterns are believed not to be possible. For fractional wavelengths,
(λ/2n, n=1,2 . . . ) the intensity in the interference pattern
decreases rapidly as n increases and the ability to differentiate weak
interference patterns from the background decreases accordingly.

[0051]When the lipid film thickness falls below about 90 nm, no color is
seen in the image generated by the present apparatus (employing the
current LED light source), only gray of varying density. It is presumed
that violet and ultraviolet interference effects predominate at this
thickness, but since they are absent from the incident spectrum, no color
can be seen. Any interference remaining over the visible light spectrum
is so weak due to the very small fraction (λ/2n, n>5) that
full-spectrum reflection and absorption effects dominate and no
particular color can be seen. Broadband destructive interference in the
60-75 nm layers gives way to broadband constructive interference at the
thinnest layer (<=30 nm).

[0052]In summary, it is believed that the present invention demonstrates
the results of subtractive colors, where subtracting the blue end from
white light leaves a reddish tint, subtracting the center (yellow-green)
from the spectrum leaves a brownish tint, and subtracting orange-red
leaves a blue tint. Because all the interference patterns are fractional
wavelengths, and therefore relatively weak in intensity, the images are
not strongly saturated. Image enhancement techniques therefore assume a
higher importance for good visibility. Film thickness below about 90 nm
can be determined by gray scale analysis.

[0053]Should the use of real time or high speed data transfer and large
storage volumes be required for a given application, the use of a means
for recording the output signal representative of the specularly
reflected light (video output signal) such as a high performance computer
system would be needed. As employed herein, the term "real time" is
defined as data transfer, storage and retrieval at a rate required for
image generation that the observer requires for a subjectively
satisfactory viewing experience. For viewing the motion of the lipid
layer interference pattern after blinking a minimum of about 15 frames
per second is satisfactory for seamless motion perception. Depending upon
settings, the camera can create 1.4-3.9 MB images at 15 per second, or
21-57 MB/sec which must be processed by the computer for storage,
display, or computation. At this rate, one minute of recording requires
1.26-3.42 GB of storage. Given the presently available technology, it is
not reasonable to store recording sessions in RAM, so the data from the
camera must be streamed directly to a storage system sized to meet the
anticipated volume of data. For example, 500 GB of storage could record
147-397 tests of one minute duration. Various forms of data management
could be applied to reduce the storage requirements, including image
size, compression, and minimizing recording time adequate to good
diagnostics.

[0054]The software to operate the camera, capture the images, store and
retrieve image files, and execute chosen calculations on the data is
critical to the success of the system. Relevant specifications are:

[0055]The mechanical system consists of components to position the
patient's head, position the illuminator and camera, focus the camera,
and switch position between eyes.

[0056]Current ophthalmic chin rests are adequate for positioning and
restraining the head. They include vertical (Z axis) adjustment.

[0057]A movable frame positions the camera and illuminator opposite the
patient's face. The illuminator and camera move together in a gross
manner, but the illuminator has an independent X and rotational motions
for accommodating different facial geometries. Switching from eye to eye
requires moving the whole camera/illuminator frame away from the patients
face (X motion) and horizontally to line up with the second eye (Y
motion). Focusing the camera requires fine control of X motion, and
vertical Z motion is required to accommodate differences in patient eye
positions. A classical slit lamp biomicroscope stand incorporates most of
these motions, and have added angular motions not needed in the present
system.

[0058]FIGS. 1, 2, 3a-3b illustrate the full-eye system. A typical
examination session proceeds as follows: [0059]Presets: The vertical
relationship between the camera and the illuminator is set. For a
half-eye illuminator, the camera position is just enough higher than the
illuminator top edge that the image contains no edge effects. When using
the full-eye illuminator, the camera is positioned coaxially with the
hole through the illuminator. The camera/illuminator position should not
need adjusting thereafter.

[0060]Patient examination: [0061]1. The patient is seated and asked to
place their chin on the chin rest. The chin rest is adjusted (Z axis) for
the comfort of the patient. The patient is asked to hold their forehead
against the forehead rest. [0062]2. The frame holding the camera &
illumination is positioned on the axis of the first eye and brought close
enough for rough focus on the skin. [0063]3. The frame is adjusted for
vertical and horizontal centering, and then moved forward for fine
focusing. [0064]4. The illuminator is adjusted forward and back, and
rotated for best illumination of the eye. Repeat fine focus as necessary.
The patient is asked to look directly at the center or top center of the
camera lens. Instructions are given to the patient for blinking regimens
by the diagnostician. It will be noted that measurement is taken when the
patient is not blinking, but that this interval is between the previous
blink and before the next blink. Therefore, as employed herein the terms
"after blinking" and "before blinking" are somewhat interchangeable as
they both refer to the substantially non-eyelid moving period of time
"between blinks". [0065]5. The images are viewed and recorded as desired.
[0066]6. The frame may be pulled away from the patient (to clear the
nose) and moved horizontally to the next eye. Steps 2.-5 are repeated.

[0067]The system could be fully motorized and operated in manual,
semi-autonomous, or autonomous modes, depending upon the sophistication
of the control software. A fully automatic system would adjust the
mechanical stand, focus the camera, record the motion of the lipid film,
calculate various measurements of the film structure, report an
assessment of the quality of the lipid film, and record the data in the
patient's record file.

[0068]The invention having been thus disclosed, diverse changes and
variation in the apparatus and method will occur to those skilled in the
art, and all such changes and modifications are intended to be within the
scope of the invention, as set forth in the following claims: